KRAS Hijacks the miRNA Regulatory Pathway in Cancer

Authors

Angelina S Bortoletto
Ronald J Parchem

Publication Date

5-15-2023

Journal

Cancer Research

DOI

10.1158/0008-5472.CAN-23-0296

PMID

36946612

PMCID

PMC10183808

PubMedCentral® Posted Date

3-22-2023

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Humans, Cell Transformation, Neoplastic, MicroRNAs, Mutation, Neoplasms, Proto-Oncogene Proteins p21(ras)

Abstract

Extensive studies have focused on the misregulation of individual miRNAs in cancer. More recently, mutations in the miRNA biogenesis and processing machinery have been implicated in several malignancies. Such mutations can lead to global miRNA misregulation, which may promote many of the well-known hallmarks of cancer. Interestingly, recent evidence also suggests that oncogenic Kristen rat sarcoma viral oncogene homolog (KRAS) mutations act in part by modulating the activity of members of the miRNA regulatory pathway. Here, we highlight the vital role mutations in the miRNA core machinery play in promoting malignant transformation. Furthermore, we discuss how mutant KRAS can simultaneously impact multiple steps of miRNA processing and function to promote tumorigenesis. Although the ability of KRAS to hijack the miRNA regulatory pathway adds a layer of complexity to its oncogenic nature, it also provides a potential therapeutic avenue that has yet to be exploited in the clinic. Moreover, concurrent targeting of mutant KRAS and members of the miRNA core machinery represents a potential strategy for treating cancer.